In the skin, different sensory qualities interact competitively with one another (Schmidt R F (1971). Presynaptic inhibition in the vertebrate central nervous system. Ergebn. Physiol. 63:20-101; Melzack R et al. (1965). Pain mechanisms: a new theory. A gate control system modulates sensory input from the skin before it evokes pain perception and response. Science 150: 971-979; McMahon S B et al. (1992). Itching for an explanation. Trends in Neurosci. 15/12:497-501; Ward L et al. (1996). A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain. Pain 64:129-138). Mechanical stimulation inhibits ongoing pain (Wall P D et al. (1960). Pain, itch, and vibration, A.M.A. Archives of Neurology 2:365-375; Sjölund B H et al. (1990). Transcutaneous and implanted electric stimulation of peripheral nerves. In: J. Bonica (ed): Management of Pain, 2nd edition, Lea & Fegiber, Philadelphia, p 1852-1861)). To utilize the interactions between tactile and pain pathways, transcutaneous electrical nerve stimulation (TENS) was developed in the seventies (Flowerdew et al. (1997); Osiri et al, (2003)). This method uses surface electrodes that are attached to the skin overlying the nerve to be stimulated. Stimulation intensity is such that mainly the large nerve fibers, classified as Aβ fibers, carrying tactile information, are activated. Different forms of TENS are known and are frequently used in the clinic. Conventional TENS uses high frequency stimulation of tactile Aβ fibers. Another form of TENS was later developed to activate deep afferents from the muscles (Sjölund et al. 1990). In this case, TENS is given with a low frequency at an intensity that cause muscle contraction. Both methods have been shown to produce analgesia, although the mechanisms of action appear to be different (Sjölund et al. 1990). TENS is, however, not suitable for the stimulation of unmyelinated fibers classified as C fibers. Using TENS, the threshold current needed to activate C fibers is very high and thus cannot be tolerated. Clinical effects of TENS are summarized by Flowerdew and Goadsby (1997), Osiri et al (2003).
Particularly strong interactions are found between submodalities of the nociceptive system (here including itch), e.g. low frequency electrical stimulation of Aδ/C fibers, i.e. thin myelinated fibers and non-myelinated fibers, respectively, may cause a durable depression of nociceptive C fiber transmission both in vivo (Sjölund B H (1985). Peripheral nerve stimulation suppression of C-fiber-evoked flexion reflex in rats. Part 1: parameters of continuous stimulation. J. Neurosurg. 63:612-616; Sjölund B H (1988). Peripheral nerve stimulation suppression of C-fiber-evoked flexion reflex in rats. Part 2: parameters of low-rate train stimulation of skin and muscle afferent nerves. J. Neurosurg. 68:279-283; Klein T et al. (2004). Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans. J. Neurosci. 24:964-71) and in vitro spinal preparations (Sandkühler et al., 1997). Furthermore, noxious mechanical stimulation that strongly activates tactile Aβ and nociceptive C fibers, such as scratching, reduces itch. These interactions occur at several levels in the somatosensory system, e.g. the dorsal horn of the spinal cord (Melzack et al. (1965); Cervero F et al. (1979). An electrophysiological study of neurones in the substantia gelatinosa rolandi of the cat's spinal cord. Quart. J. Exp. Physiol. 64:297-314) and the thalamus (Olausson B et al. (1994). Dorsal column inhibition of nociceptive thalamic cells mediated by gamma-aminobutyric acid mechanisms in the cat. Acta Physiol. Scand. 152: 239-247.), and are often topographically well organized. It is therefore important to stimulate local areas that are related to the itchy or painful body part.
To enable stimulation of thin afferent fibers, including Aδ and C fibers for the relief of itch and pain, a new technique, termed Cutaneous Field Stimulation (CFS), was introduced (Schouenborg, 1995; Nilsson et al, 1997, Nilsson and Schouenborg, 1999; Nilsson et al, 2003, 2004). CFS allows topographically restricted and tolerable electrical stimulation of thin (Aδ and C) cutaneous fibers but is not useful for the stimulation of Aβ fibers. CFS uses a flexible rubber plate with multi-array needle-like electrodes regularly fixed at 2-cm intervals. Each electrode is surrounded by an elevated “stop-device” about 2.0 mm in diameter that protrudes 2.0 mm from the plate. The electrode tip usually protrudes 0.3 mm from the stop-device. When gently pressing the electrode plate against the skin, the electrode tips are introduced close to the receptors in the epidermis and the superficial part of dermis (Kruger et al, 1985). Since the electrodes traverse the electrically isolating horny layer of the epidermis and the current density is high near the sharp electrode tips, the voltage and current required for stimulating cutaneous nerve fibers are small, typically less than 10 V and up to 0.8 mA, respectively. As the current density decreases rapidly with distance, localized stimulation is achieved. The electrodes are stimulated consecutively with a constant current stimulator, each electrode with a frequency of 1-10 Hz (pulse duration 1.0 ms) and treatment duration of 5-45 min. A self-adhesive surface (TENS) electrode serves as anode and is usually placed about 5-30 cm away from the needle electrode plate. Clinical effects of CFS have been summarized by Nilsson et al., 2004.
Arrays of needles on stiff electrode plates are known in the art. In these cases there are no means of controlling skin indentation other than the length of the needles. Due to the fact that most body parts are curved; such electrode plates usually do not allow controlled skin penetration of multiple needle electrodes to a defined skin depth.
Shortcomings of the Present Technology
1. Given the strong interactions between different sensory modalities and the strong effects of Aδ/C fibers it would be a considerable advantage to combine effective Aβ fiber stimulation (such as TENS) and Aδ/C fiber stimulation (such as CFS) in the same equipment. Then the aversiveness of Aδ/C fiber stimulation could be masked by concurrent A/β fiber stimulation. There is, however, no known method that combines an effective stimulation of Aβ fibers at multiple plates and in a tolerable way, with consecutive stimulation of Aδ/C fibers with a pattern of needle-like electrodes within a defined skin area. Moreover, there is no known method to combine TENS and CFS in one treatment.
2. During the onset of CFS, a pricking pain sensation is elicited. While being tolerable it is initially uncomfortable and this may reduce compliance in children and persons with sensitive skin. Existing techniques have no solution to this problem other than a gradual increase in stimulation intensity.
3. Known devices for cutaneous Aδ/C fiber stimulation are not easily applied to the skin. For example, the CFS technique utilizes a bandage to attach the electrode plate to the skin. In some situations this is impractical and thus reduces patient compliance. A method that enables easy attachment of the electrode ensemble and that at the same time keep the electrode tips at a defined depth in the skin without taking recourse to a bandage would be a considerable improvement.
4. Known methods for multi-channel electrode stimulation of Aδ/C fibers use an electrode plate that does not allow moisture from the skin area covered by the plate to evaporate. This results in accumulation of moisture between the plate and the skin. This can short-circuit the electric pulses between the active electrodes and the reference electrode. Furthermore, it prevents long-term use of the electrode plate under, for instance, a plaster of Paris. Since the skin often becomes very itchy under a plaster of Paris, this is an obvious shortcoming.
5. Electrodes known in the art protruding from the CFS plate as disclosed in WO 93/23112, granted to European Patent No. 1993910490 on Aug. 14, 1996, are made of a conducting material that is different from that of the stop device that surrounds the electrode. This arrangement decreases the precision with which the length of the protruding electrode tips are made during manufacture. As is it important to control the depth in the skin, this is a clear disadvantage.